Calcium Modulation of Cyclic GMP Synthesis in Rat Visual Cells

The synthesis of cyclic GMP in dark-adapted rat retinas, retinal homogenates or isolated ROS is stimulated during incubation with medium containing low levels of Ca2+. The guanylate cyclase that is stimulated by low [Ca2+] is localized exclusively in visual cells of the retina because the stimulatory effect of low [Ca2+] is observed in developing retinas only after visual cells begin to differentiate, and it is lost in diseased retinas when the photoreceptor cells degenerate. The accumulation of cyclic GMP during incubation with low [Ca/+] is prevented by illumination; the effect of light stems apparently from the light-enhanced hydrolysis of cyclic GMP. Following light adaptation and transfer of the animals to darkness, retinas become progressively more responsive to low [Ca2+], and a maximal response is restored after about 30 min of dark adaptation in vivo. Incubated retinas accumulate cyclic GMP when exposed to media containing less than about 5 x 10(-9) M [Ca2+], whereas the synthesis of cyclic GMP in retinal homogenates or lysed ROS is stimulated at concentrations of less than 10(-6) M-Ca2+. These findings indicate that calcium acts as an inhibitory effector in the regulation of guanylate cyclase in rod photoreceptor cells, and they suggest that changes in intracellular [Ca2+] may regulate the synthesis of cyclic GMP in dark-adapted visual cells in situ.